CA1211049A - Gelatine capsule - Google Patents
Gelatine capsuleInfo
- Publication number
- CA1211049A CA1211049A CA000448594A CA448594A CA1211049A CA 1211049 A CA1211049 A CA 1211049A CA 000448594 A CA000448594 A CA 000448594A CA 448594 A CA448594 A CA 448594A CA 1211049 A CA1211049 A CA 1211049A
- Authority
- CA
- Canada
- Prior art keywords
- weight
- sorbitol
- dosage unit
- unit form
- sorbitan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
- A61K9/4825—Proteins, e.g. gelatin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A pharmaceutical dosage unit form comprises one or more pharmaceutically active materials dissolved or suspended in a liquid polyethylene glycol and encapsulated in a soft gelatin cap-sule shell, in which the capsule shell comprises gelatin, a plastic-izer therefor, and an embrittlement inhibiting composition compris-ing a mixture of sorbitol and at least one sorbitan. Preferably the polyethylene glycol also contains glycerin, sorbitol or propy-lene glycol.
A pharmaceutical dosage unit form comprises one or more pharmaceutically active materials dissolved or suspended in a liquid polyethylene glycol and encapsulated in a soft gelatin cap-sule shell, in which the capsule shell comprises gelatin, a plastic-izer therefor, and an embrittlement inhibiting composition compris-ing a mixture of sorbitol and at least one sorbitan. Preferably the polyethylene glycol also contains glycerin, sorbitol or propy-lene glycol.
Description
BACKGROUND OF THE INVENTION
Field of the Invention and Description of the Prior Art This invention is concerned with improvements in and relating to 5 pharmaceutical compositions and, more particularly, is concerned with pharmaceutical compositions in dosage unit form encapsulated in soft gelatin capsules.
Pharmaceutical compositions in dosage unit form encapsulated in soft gelatin capsules thereinafter simply referred to as "capsules") are 10 well known and basically consist of a 'fill", comprising one or more pharmaceutically active materials dissolved or dispersed in an appropriate liquid vehicle, encapsulated in a soft gelatin shell, generally comprising - gelatin together with a plasticizer therefore such as glycerin.
class of vehicle which has been proposed for use in the fill 15 comprises the liquid polyethylene glycols, for example polyethylene glycols having a molecular weight from about to 600. Certain pharmaceutically active ingredients, for example benzodiazepine type compounds such as temazepam and lormeta~epam, have been shown to have improved bioavailability when administered as polyethylene glycol 2û solutions in soft capsules.
However, the use OX a liquid polyethylene glycol as a carrier vehicle has an attendant disadvantage in that the material is hydroscopic end tends to absorb water from the shell and thereby em brittle it. This embrittlement may be enhanced by migration of the plasticizer from the 25 shell into the fill As a rest of such embrittlement, which may take place over a matter of months or years, the Shea loses its elasticity and, hence its resistance to mechanical shocks which are, encountered in handling and transport of the capsules. In extreme cases the capsules may be sufficiently embrittled and/or suffer such mechanical shocks that a on capsule is ruptured.
The problem is not so severe as to render capsules having a fill comprising a liquid polyethylene glycol vehicle useless. Many thousands, or indeed millions, of such capsules survive transport and handling without breakage. However, the problem does exist and is exacerbated by the 35 fact that, since capsules are commonly packed together in several tens, I
hlmdreds or even thousands, one breaking, and therefore leaking, capsule can damage other capsules in the same package and thus render a large number of capsules useless.
0~9 SUMMARY OF THE INVENTION
_ It has now been found, in accordance with the present invention, that the problem of embri-ttlement may be reduced by incorporating in the shell sorbitol in admixture with at least one sorbitan and, possibly, other polyols, and at the same time incur-prorating glycerin, sorbitol or propylene glycol in the liquid polyp ethylene glycol vehicle of the fill of the capsules.
DETAILED DESCRIPTION OF THE
PREFERRED EMBODIMENT
Accordingly, the invention provides a pharmaceutical doss age unit form comprising one or more pharmaceutically active mate-fiats dissolved or suspended in a liquid polyethylene glycol and encapsulated in a soft gelatin capsule shell, in which the capsule ; shell comprises gelatin, a plasticizer therefore and an em brittle-mint inhibiting composition comprising a mixture of sorbitol and at least one sorbitan.
Typically, the embrittlement inhibiting composition come proses from 25 to 45% by weight of sorbitol and from 20 to 30% by weight ox sorbitans (the major proportion of the sorbitan coupon-en being l,4-sorbitan) together with water (typically in an amount of 13 to 20% by weight) and at least one polyhydric alcohol other than sorbitol, the minutely content being from 0 to I% by weight Preferably the polyethylene glycol also contains glycerin, sorbitol or propylene glycol~ In this case, the amount of glycerin, sorbitol or propylene glycol dissolved in the liquid polyethylene-glycol fill is suitably from 1 to 20% by weight, pro-fireball from 3 to 12% by weight, more preferably from 3 to I% by weight.
',~;
The amount of sorbitol/sorbitan(s) mixture in the shell is suitably from 4 to 25% by weight, preferably from 6 to 20% by weight more preferably from g to 15% by weight.
As noted above, the sorbitol/sorbitan(s) mixture may con-lain other polyhydric alcohols but in this case the total amount of orbital and sorbitan(s) in the whole sorbitol/sorbitan(s)/other polyhydric alcohol(s) mixture is suitably from I to 75% by weight, preferably from 55 to I by weight The other polyhydric alcohols are suitably hydrogenated saccharides.
The total mixture suitably contains not more than 6% by weight of minutely and preferably contains from 1 to 4% by weight, more preferably from 2 to I by weight of minutely.
Suitable materials for introducing the sorbitol/
sorbitan(s)/polyhydric alcohol(s) mixture into the capsule shell are concentrated aqueous solutions of polyhydric alcohols derived from the hydrolysis and partial hydrogenation of glucose syrup.
An example of a suitable commercially Roy I
available material is that sold under the Trade mark "Anidrisorb 85/70" (a product manufactured by Coquette Frees, located at Rue Pa-ton, Lisle, France). This product has the typical analysis listed below:
Components (% by weight of concentrated aqueous solutions):
D Sorbitol Sorbitans Other polyols ~annitol Water 25-45% 20-30% 20-25% 0-6% 13-20%
In addition to the sorbitol/sorbitan(s) mixture, the gelatin material of the capsule shell will also contain a plasticizer, such as glycerin, propylene glycol or sorbitol (in addition to the sorbitol in the sorbitol/sorbitane mixture), and this is suitably present in an amount of from 10 to 40% by weight, preferably from 25 to 35% by weight. Further the shell material may contain other conventional ingredients such as coloring agents (pigments or distaffs), and oxidant or preservative materials such as potassium sorb ate and ethyl, methyl and propel parabens.
The pharmaceutically active component of the compositions of the invention may be any of a wide variety of orally ad minis-treble pharmaceutical materials. Where the material is insuf~ic-gently soluble in the liquid polyethylene glycol vehicle, the fill may contain co-solvents, such as water or ethanol, or suspending or dispersing agents. Preferably, however, the pharmaceutical material is one soluble in the liquid polyethylene glycol vehicle such as the benzodiazepines type compounds mentioned above.
In order that the invention may be well understood the following examples are given by way of illustration only.
owe Soft gelatin capsules were produced having the fill composition and shell composition noted below.
Example 1 Temazepam Capsules, 10 my (a) Fill composition in my per capsule Temazepam 10 my Polyethylene glycol 400 230 my Glycerin 13 my - pa -I
LO
I, (by Dry Shell Composition (% by weight) Gelatin I
Glycerin 32%
Anidrisorb ~5/70 12%
Water 5%
Example 2 Temazepam Capsules, 20 my (a) Fill Composition in my eon capsule Temazepam 20 my Polyethylene glycol 460 my Glycerin 26 my (b) Gelatin I
Glycerin 32%
Anidrisorb 3~/70 1296 Water 5~6 Exhume Lormetazepam Coppices, 0.5 my (a) Fill composition in my per capsule Lormetazepam 0.5 my Polyethylene glycol 1:l5 my Glycerin 6.5 my (by Dry Shell Causation Gelatin 51%
Glycerin 32%
Anidrisorb ~5/70 12%
Water 5%
Example 4 Lormetazepam Capsules, 1 my I (a) Jill Composition in my per capsule Lormetazepam 1 my Polyethylene glycol 230 my Glycerin 13 my I
(b) Dry Shell Composition % by weight Gelatin 51%
f Glycerin go 32%
~'~ Anidrisorb ~/70 12%
Water 5%
Examples 5 and 6 Sot elastic gelatin capsules were produced from a fluid gelatin composition comprising (in % by weight):
Gelatin 38.5%
Glycerol I 20.796 Anidrisorb ~/70 8.8%
Water 32.0%
filled with a liquid fill comprising (in % by weight:
Temazepam 3.92%
Polyethylene glycol 400 96.08%
Two batches of capsules were produced the first (Example 5) containing 10 my of Temazepam per capsule and the second example 6 containing 2û my of Temazepam per capsule.
By way of comparison, gelatin capsules were produced using the 20 same fill but using a conventional shell forming composition comprising (in % by weight):
Gelatin 42.06%
Glycerol 24.30%
Water 33.64%
25 Again two batches of coppices were produced, the first (Comparative Example I containing 10 my ox Temazepam per capsule and the second (Comparative Employ 2) containing 20 my of Temazepam per capsule.
The batches of capsules were stored at 20V C for several months and 30 the hardness of samples of the batches was tested at intervals using a lea I s is Hardness tester. Basically, this instrument operates by compressing the capsule under test for 20 seconds between a plunger attached to a load cell and a platform which is automatically raised.
Thus, in order to test a capsule, it is placed horizontally on the platform 35 so that it is in contact with both the platform and the plunger. During the Lo g test, the platform rises automatically and the load cell indicator displays the value of the resistance of the capsule to the compressive force. After 20 seconds the test is completed and the value displayed represents the hardness of the capsule under test.
In practice it has been found as a matter of experience, that a hardness of greater than 12 Newtons measured as described above, indicates that breakage through embrittlement of the capsule may be expected as a particular problem.
The resldts of the tests are shown in Table 1.
Table 1 Hardness (Newtons stored at 20C for I- ' Example 0 1.7 7.8 9.8 month months months months months 8.0 go 11.5 -I 12.3 15 6 5.25 8.0 10.4 11.2 11.9 Camp 1 9.95 11.65 13.75 13.65 13.75 Coup. 2 7.3 10.5 12.75 13.25 13.2 It may be seen from these results that the capsules in accordance with the invention have generally lower initial harnesses than 20 comparable corrected coppices and that they have effective storage lives, considered as lives during which their hardness is 12 or less, at least twice as long US those of the comparable conventional capsules.
Examples 7 and 8 Soft elastic gelatin capsules were produced from a fluid gelatin composition comprising (in % by White ~;
Gelatin 4B~
Glycerol 13.02%
Anidrisorb ~;/70 7.53%
Water 33.58%
filled with fill comprising (in % by weight)-Temazepam yo-yo Glycerol 5.0,6f Water Polyethylene glycol 400 90.2%
"
Two batches of capsules were prepared one (Example 7) containing 10 my of per capsule and the other (Example I containing 20 my of temazepam per keeps.
The batches were divided into three lots and each lot was stored at 5 a temperature of 20C, 30C, and 40C, respectively. The hardness of the coppices were determined as described in Examples 5 and 6 to give the rests shown in Table 2.
Table 2 Hardness (Newtons) stored or Example (storage tempera- 0 month 1 month 3.5 months lure - C) 7(20) 7.93 - 10.60 7(30) 7.g3 - 11~32 7(40) 7.92 11.34 10.43 lo 8(20) 6.91 - 10.22 8(30) 6.91 - 11.23 8(40) 6.91 10.20 11.05
Field of the Invention and Description of the Prior Art This invention is concerned with improvements in and relating to 5 pharmaceutical compositions and, more particularly, is concerned with pharmaceutical compositions in dosage unit form encapsulated in soft gelatin capsules.
Pharmaceutical compositions in dosage unit form encapsulated in soft gelatin capsules thereinafter simply referred to as "capsules") are 10 well known and basically consist of a 'fill", comprising one or more pharmaceutically active materials dissolved or dispersed in an appropriate liquid vehicle, encapsulated in a soft gelatin shell, generally comprising - gelatin together with a plasticizer therefore such as glycerin.
class of vehicle which has been proposed for use in the fill 15 comprises the liquid polyethylene glycols, for example polyethylene glycols having a molecular weight from about to 600. Certain pharmaceutically active ingredients, for example benzodiazepine type compounds such as temazepam and lormeta~epam, have been shown to have improved bioavailability when administered as polyethylene glycol 2û solutions in soft capsules.
However, the use OX a liquid polyethylene glycol as a carrier vehicle has an attendant disadvantage in that the material is hydroscopic end tends to absorb water from the shell and thereby em brittle it. This embrittlement may be enhanced by migration of the plasticizer from the 25 shell into the fill As a rest of such embrittlement, which may take place over a matter of months or years, the Shea loses its elasticity and, hence its resistance to mechanical shocks which are, encountered in handling and transport of the capsules. In extreme cases the capsules may be sufficiently embrittled and/or suffer such mechanical shocks that a on capsule is ruptured.
The problem is not so severe as to render capsules having a fill comprising a liquid polyethylene glycol vehicle useless. Many thousands, or indeed millions, of such capsules survive transport and handling without breakage. However, the problem does exist and is exacerbated by the 35 fact that, since capsules are commonly packed together in several tens, I
hlmdreds or even thousands, one breaking, and therefore leaking, capsule can damage other capsules in the same package and thus render a large number of capsules useless.
0~9 SUMMARY OF THE INVENTION
_ It has now been found, in accordance with the present invention, that the problem of embri-ttlement may be reduced by incorporating in the shell sorbitol in admixture with at least one sorbitan and, possibly, other polyols, and at the same time incur-prorating glycerin, sorbitol or propylene glycol in the liquid polyp ethylene glycol vehicle of the fill of the capsules.
DETAILED DESCRIPTION OF THE
PREFERRED EMBODIMENT
Accordingly, the invention provides a pharmaceutical doss age unit form comprising one or more pharmaceutically active mate-fiats dissolved or suspended in a liquid polyethylene glycol and encapsulated in a soft gelatin capsule shell, in which the capsule ; shell comprises gelatin, a plasticizer therefore and an em brittle-mint inhibiting composition comprising a mixture of sorbitol and at least one sorbitan.
Typically, the embrittlement inhibiting composition come proses from 25 to 45% by weight of sorbitol and from 20 to 30% by weight ox sorbitans (the major proportion of the sorbitan coupon-en being l,4-sorbitan) together with water (typically in an amount of 13 to 20% by weight) and at least one polyhydric alcohol other than sorbitol, the minutely content being from 0 to I% by weight Preferably the polyethylene glycol also contains glycerin, sorbitol or propylene glycol~ In this case, the amount of glycerin, sorbitol or propylene glycol dissolved in the liquid polyethylene-glycol fill is suitably from 1 to 20% by weight, pro-fireball from 3 to 12% by weight, more preferably from 3 to I% by weight.
',~;
The amount of sorbitol/sorbitan(s) mixture in the shell is suitably from 4 to 25% by weight, preferably from 6 to 20% by weight more preferably from g to 15% by weight.
As noted above, the sorbitol/sorbitan(s) mixture may con-lain other polyhydric alcohols but in this case the total amount of orbital and sorbitan(s) in the whole sorbitol/sorbitan(s)/other polyhydric alcohol(s) mixture is suitably from I to 75% by weight, preferably from 55 to I by weight The other polyhydric alcohols are suitably hydrogenated saccharides.
The total mixture suitably contains not more than 6% by weight of minutely and preferably contains from 1 to 4% by weight, more preferably from 2 to I by weight of minutely.
Suitable materials for introducing the sorbitol/
sorbitan(s)/polyhydric alcohol(s) mixture into the capsule shell are concentrated aqueous solutions of polyhydric alcohols derived from the hydrolysis and partial hydrogenation of glucose syrup.
An example of a suitable commercially Roy I
available material is that sold under the Trade mark "Anidrisorb 85/70" (a product manufactured by Coquette Frees, located at Rue Pa-ton, Lisle, France). This product has the typical analysis listed below:
Components (% by weight of concentrated aqueous solutions):
D Sorbitol Sorbitans Other polyols ~annitol Water 25-45% 20-30% 20-25% 0-6% 13-20%
In addition to the sorbitol/sorbitan(s) mixture, the gelatin material of the capsule shell will also contain a plasticizer, such as glycerin, propylene glycol or sorbitol (in addition to the sorbitol in the sorbitol/sorbitane mixture), and this is suitably present in an amount of from 10 to 40% by weight, preferably from 25 to 35% by weight. Further the shell material may contain other conventional ingredients such as coloring agents (pigments or distaffs), and oxidant or preservative materials such as potassium sorb ate and ethyl, methyl and propel parabens.
The pharmaceutically active component of the compositions of the invention may be any of a wide variety of orally ad minis-treble pharmaceutical materials. Where the material is insuf~ic-gently soluble in the liquid polyethylene glycol vehicle, the fill may contain co-solvents, such as water or ethanol, or suspending or dispersing agents. Preferably, however, the pharmaceutical material is one soluble in the liquid polyethylene glycol vehicle such as the benzodiazepines type compounds mentioned above.
In order that the invention may be well understood the following examples are given by way of illustration only.
owe Soft gelatin capsules were produced having the fill composition and shell composition noted below.
Example 1 Temazepam Capsules, 10 my (a) Fill composition in my per capsule Temazepam 10 my Polyethylene glycol 400 230 my Glycerin 13 my - pa -I
LO
I, (by Dry Shell Composition (% by weight) Gelatin I
Glycerin 32%
Anidrisorb ~5/70 12%
Water 5%
Example 2 Temazepam Capsules, 20 my (a) Fill Composition in my eon capsule Temazepam 20 my Polyethylene glycol 460 my Glycerin 26 my (b) Gelatin I
Glycerin 32%
Anidrisorb 3~/70 1296 Water 5~6 Exhume Lormetazepam Coppices, 0.5 my (a) Fill composition in my per capsule Lormetazepam 0.5 my Polyethylene glycol 1:l5 my Glycerin 6.5 my (by Dry Shell Causation Gelatin 51%
Glycerin 32%
Anidrisorb ~5/70 12%
Water 5%
Example 4 Lormetazepam Capsules, 1 my I (a) Jill Composition in my per capsule Lormetazepam 1 my Polyethylene glycol 230 my Glycerin 13 my I
(b) Dry Shell Composition % by weight Gelatin 51%
f Glycerin go 32%
~'~ Anidrisorb ~/70 12%
Water 5%
Examples 5 and 6 Sot elastic gelatin capsules were produced from a fluid gelatin composition comprising (in % by weight):
Gelatin 38.5%
Glycerol I 20.796 Anidrisorb ~/70 8.8%
Water 32.0%
filled with a liquid fill comprising (in % by weight:
Temazepam 3.92%
Polyethylene glycol 400 96.08%
Two batches of capsules were produced the first (Example 5) containing 10 my of Temazepam per capsule and the second example 6 containing 2û my of Temazepam per capsule.
By way of comparison, gelatin capsules were produced using the 20 same fill but using a conventional shell forming composition comprising (in % by weight):
Gelatin 42.06%
Glycerol 24.30%
Water 33.64%
25 Again two batches of coppices were produced, the first (Comparative Example I containing 10 my ox Temazepam per capsule and the second (Comparative Employ 2) containing 20 my of Temazepam per capsule.
The batches of capsules were stored at 20V C for several months and 30 the hardness of samples of the batches was tested at intervals using a lea I s is Hardness tester. Basically, this instrument operates by compressing the capsule under test for 20 seconds between a plunger attached to a load cell and a platform which is automatically raised.
Thus, in order to test a capsule, it is placed horizontally on the platform 35 so that it is in contact with both the platform and the plunger. During the Lo g test, the platform rises automatically and the load cell indicator displays the value of the resistance of the capsule to the compressive force. After 20 seconds the test is completed and the value displayed represents the hardness of the capsule under test.
In practice it has been found as a matter of experience, that a hardness of greater than 12 Newtons measured as described above, indicates that breakage through embrittlement of the capsule may be expected as a particular problem.
The resldts of the tests are shown in Table 1.
Table 1 Hardness (Newtons stored at 20C for I- ' Example 0 1.7 7.8 9.8 month months months months months 8.0 go 11.5 -I 12.3 15 6 5.25 8.0 10.4 11.2 11.9 Camp 1 9.95 11.65 13.75 13.65 13.75 Coup. 2 7.3 10.5 12.75 13.25 13.2 It may be seen from these results that the capsules in accordance with the invention have generally lower initial harnesses than 20 comparable corrected coppices and that they have effective storage lives, considered as lives during which their hardness is 12 or less, at least twice as long US those of the comparable conventional capsules.
Examples 7 and 8 Soft elastic gelatin capsules were produced from a fluid gelatin composition comprising (in % by White ~;
Gelatin 4B~
Glycerol 13.02%
Anidrisorb ~;/70 7.53%
Water 33.58%
filled with fill comprising (in % by weight)-Temazepam yo-yo Glycerol 5.0,6f Water Polyethylene glycol 400 90.2%
"
Two batches of capsules were prepared one (Example 7) containing 10 my of per capsule and the other (Example I containing 20 my of temazepam per keeps.
The batches were divided into three lots and each lot was stored at 5 a temperature of 20C, 30C, and 40C, respectively. The hardness of the coppices were determined as described in Examples 5 and 6 to give the rests shown in Table 2.
Table 2 Hardness (Newtons) stored or Example (storage tempera- 0 month 1 month 3.5 months lure - C) 7(20) 7.93 - 10.60 7(30) 7.g3 - 11~32 7(40) 7.92 11.34 10.43 lo 8(20) 6.91 - 10.22 8(30) 6.91 - 11.23 8(40) 6.91 10.20 11.05
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A pharmaceutical dosage unit form comprising at least one pharmaceutically active material dissolved or suspended in a liquid polyethylene glycol and encapsulated in a soft gelatin capsule shell, in which the capsule shell comprises gelatin, a plasticizer therefor and an embrittlement inhibiting composition comprising a mixture of sorbitol and at least one sorbitan.
2. A dosage unit form as claimed in claim 1 in which the embrittlement inhibiting composition comprises from 25 to 45%
by weight of sorbitol and from 20 to 30% by weight of sorbitan together with water and at least one polyhydric alcohol other than sorbitol.
by weight of sorbitol and from 20 to 30% by weight of sorbitan together with water and at least one polyhydric alcohol other than sorbitol.
3. A dosage unit form as claimed in claim 2, in which the embrittlement inhibiting composition contains not more than 6% by weight of mannitol.
4. A dosage unit form as claimed in claim 1 in which the shell contains from 4 to 25% by weight of the sorbitol/sorbitan mixture.
5. A dosage unit form as claimed in claim 1 in which the polyethylene glycol also contains glycerin, sorbitol or propylene glycol.
6. A dosage unit form as claimed in claim 5 in which the glycerin, sorbitol or propylene glycol is present in the polyethylene glycol in an amount of from 1 to 20% by weight.
7. A pharmaceutical dosage unit form comprising at least one pharmaceutically active material, in a therapeutically effective amount, dissolved or suspended in a liquid polyethylene glycol having a mean molecular weight of from about 300 to 600 and encapsulated in a soft gelatin capsule shell, in which the capsule shell comprises gelatin, 10 to 40% by weight of a plasticizer therefor and an embrittlement inhibiting composition comprising a mixture of 25 to 45% by weight of sorbitol and 20 to 30% by weight of at least one sorbitan.
8. A dosage unit form as claimed in claim 7 in which the embrittlement inhibiting composition comprises from 25 to 45%
by weight of sorbitol and from 20 to 30% by weight of at least one sorbitan together with water and at least one polyhydric alcohol other than sorbitol.
12.
by weight of sorbitol and from 20 to 30% by weight of at least one sorbitan together with water and at least one polyhydric alcohol other than sorbitol.
12.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8305693 | 1983-03-02 | ||
| GB838305693A GB8305693D0 (en) | 1983-03-02 | 1983-03-02 | Pharmaceutical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1211049A true CA1211049A (en) | 1986-09-09 |
Family
ID=10538838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000448594A Expired CA1211049A (en) | 1983-03-02 | 1984-03-01 | Gelatine capsule |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4780316A (en) |
| EP (1) | EP0121321B1 (en) |
| JP (1) | JPH06695B2 (en) |
| KR (1) | KR890000117B1 (en) |
| AT (1) | ATE65023T1 (en) |
| AU (1) | AU566832B1 (en) |
| CA (1) | CA1211049A (en) |
| DE (1) | DE3484779D1 (en) |
| DK (1) | DK162875C (en) |
| ES (1) | ES530270A0 (en) |
| FI (1) | FI79244C (en) |
| GB (1) | GB8305693D0 (en) |
| NO (1) | NO840793L (en) |
| WO (1) | WO1984003416A1 (en) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH673947A5 (en) * | 1986-09-23 | 1990-04-30 | Sandoz Ag | |
| US5211954A (en) * | 1986-09-23 | 1993-05-18 | Sandoz Ltd. | Low dose temazepam |
| US5629310A (en) * | 1986-09-23 | 1997-05-13 | Sterling; William R. | Low dose temazepam |
| US5030632A (en) * | 1986-09-23 | 1991-07-09 | Sandoz Pharm. Corp. | Low dose temazepam |
| GB8701332D0 (en) * | 1987-01-21 | 1987-02-25 | Lilly Industries Ltd | Capsule filling |
| DE3702029A1 (en) * | 1987-01-24 | 1988-08-04 | Basf Ag | AQUEOUS OR POWDERED, WATER-DISPERSIBLE PREPARATION OF A PHARMACEUTICAL ACTIVE SUBSTANCE IN WATER-SOLUBLE AND METHOD FOR THE PRODUCTION THEREOF |
| US5447966A (en) * | 1988-07-19 | 1995-09-05 | United States Surgical Corporation | Treating bioabsorbable surgical articles by coating with glycerine, polalkyleneoxide block copolymer and gelatin |
| US4935243A (en) * | 1988-12-19 | 1990-06-19 | Pharmacaps, Inc. | Chewable, edible soft gelatin capsule |
| US5141961A (en) * | 1991-06-27 | 1992-08-25 | Richrdson-Vicks Inc. | Process for solubilizing difficulty soluble pharmaceutical actives |
| US5200191A (en) * | 1991-09-11 | 1993-04-06 | Banner Gelatin Products Corp. | Softgel manufacturing process |
| JP3121080B2 (en) * | 1991-12-19 | 2000-12-25 | アール・ピー・シーラー コーポレイション | Encapsulation solution |
| US5376688A (en) * | 1992-12-18 | 1994-12-27 | R. P. Scherer Corporation | Enhanced solubility pharmaceutical solutions |
| DE4312656C2 (en) * | 1993-04-19 | 1996-01-25 | Beiersdorf Ag | Cooling cosmetic or dermatological compositions |
| US5431916A (en) * | 1993-04-29 | 1995-07-11 | The Procter & Gamble Company | Pharmaceutical compositions and process of manufacture thereof |
| ES2308955T5 (en) * | 1993-09-28 | 2012-04-03 | R.P. Scherer Gmbh | Manufacture of soft gelatin capsules |
| US5484606A (en) * | 1994-01-24 | 1996-01-16 | The Procter & Gamble Company | Process for reducing the precipitation of difficulty soluble pharmaceutical actives |
| FR2728464B1 (en) | 1994-12-22 | 1997-04-30 | Innothera Lab Sa | UNITAL GALENIC FORM, PROCESS FOR OBTAINING SAME AND USES THEREOF |
| US5641512A (en) * | 1995-03-29 | 1997-06-24 | The Procter & Gamble Company | Soft gelatin capsule compositions |
| US5962019A (en) * | 1995-08-25 | 1999-10-05 | Sangstat Medical Corporation | Oral cyclosporin formulations |
| US5766629A (en) * | 1995-08-25 | 1998-06-16 | Sangstat Medical Corporation | Oral cyclosporin formulations |
| US6077513A (en) * | 1996-05-02 | 2000-06-20 | Massoud; Ahmed Mohamed Ali | Drug for treatment of bilharziasis (Schistosomiasis) |
| AU754712B2 (en) * | 1999-02-26 | 2002-11-21 | Shionogi & Co., Ltd. | Chewable soft capsules having improved administration properties and process for producing the same |
| US20030104048A1 (en) * | 1999-02-26 | 2003-06-05 | Lipocine, Inc. | Pharmaceutical dosage forms for highly hydrophilic materials |
| US6251426B1 (en) * | 1999-09-02 | 2001-06-26 | Banner Pharmacaps, Inc. | Ibuprofen-containing softgels |
| US6346231B1 (en) * | 1999-10-06 | 2002-02-12 | Joar Opheim | Flavored gelatin capsule and method of manufacture |
| US20030124225A1 (en) * | 1999-11-01 | 2003-07-03 | Paul West | Encapsulated alcoholic beverage |
| US20030034458A1 (en) * | 2001-03-30 | 2003-02-20 | Fuji Photo Film Co., Ltd. | Radiation image storage panel |
| US6752953B2 (en) * | 2001-12-03 | 2004-06-22 | Yung Shin Pharmaceutical Co., Ltd. | Method for manufacturing hard non-gelatin pharmaceutical capsules |
| JP4995407B2 (en) | 2002-04-25 | 2012-08-08 | バナー ファーマキャップス， インコーポレーテッド | Chewable soft capsule |
| US20050058703A1 (en) * | 2003-08-01 | 2005-03-17 | Chang Robert C. | Gelatin capsules |
| US20050230871A1 (en) * | 2004-04-20 | 2005-10-20 | Bess William S | Fast-dissolving films |
| US20060088590A1 (en) * | 2004-10-22 | 2006-04-27 | Banner Pharmacaps, Inc. | Non-blooming gelatin and non-gelatin formulations |
| US8231896B2 (en) * | 2004-11-08 | 2012-07-31 | R.P. Scherer Technologies, Llc | Non-gelatin soft capsule system |
| US20060153824A1 (en) * | 2005-01-13 | 2006-07-13 | Everett Laboratories, Inc. | Methods and kits for co-administration of nutritional supplements |
| US7485609B2 (en) * | 2005-09-29 | 2009-02-03 | Kimberly-Clark Worldwide, Inc. | Encapsulated liquid cleanser |
| US20070134493A1 (en) * | 2005-12-08 | 2007-06-14 | Kanji Meghpara | Compositions and capsules with stable hydrophilic layers |
| BRPI0707334B8 (en) | 2006-01-24 | 2021-05-25 | R Tech Ueno Ltd | soft gelatin capsule formulation of a 15-keto-prostaglandin compound and method for stabilizing a 15-ketoprostaglandin compound |
| CA2637275C (en) | 2006-01-24 | 2014-12-09 | R-Tech Ueno, Ltd. | Pharmaceutical composition comprising a bi-cyclic compound and method for stabilizing the bi-cyclic compound |
| US20090110724A1 (en) * | 2007-10-31 | 2009-04-30 | Everett Laboratories, Inc. | Compositions and methods for treatment of pain |
| EP2455071A1 (en) * | 2008-01-10 | 2012-05-23 | Takeda Pharmaceutical Company Limited | Capsule Formulation |
| US20090214641A1 (en) * | 2008-02-26 | 2009-08-27 | Joar Opheim | Sweetened Capsules for Administration |
| LT2299987T (en) | 2008-06-06 | 2018-05-25 | Boehringer Ingelheim International Gmbh | Capsule pharmaceutical dosage form comprising a suspension formulation of an indolinone derivative |
| US20170065529A1 (en) | 2015-09-09 | 2017-03-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical dosage form for immediate release of an indolinone derivative |
| US8621764B2 (en) | 2011-03-16 | 2014-01-07 | John PUCKETT | Gelatin capsule formulation and drying system |
| ITMI20110445A1 (en) * | 2011-03-22 | 2012-09-23 | Lo Li Pharma Srl | PHARMACEUTICAL FORMULATION INCLUDING INOSITOLO. |
| CN102225055B (en) * | 2011-06-14 | 2012-05-23 | 贵州地道药业有限公司 | Formula of soft capsule shell |
| CA2853965A1 (en) * | 2011-11-03 | 2013-05-10 | Gtx, Inc. | Pharmaceutical compositions of selective androgen receptor modulators and methods of use thereof |
| KR101466617B1 (en) * | 2011-11-17 | 2014-11-28 | 한미약품 주식회사 | ORAL COMPLEX FORMULATION COMPRISING OMEGA-3 FATTY ACID AND HMG-CoA REDUCTASE INHIBITOR WITH IMPROVED STABILITY |
| WO2013165789A1 (en) * | 2012-04-30 | 2013-11-07 | Dow Agrosciences Llc | Pesticide composition delivery vehicles |
| US20140271923A1 (en) | 2013-03-14 | 2014-09-18 | Christopher Brian Reid | Compositions & formulations for preventing and treating chronic diseases that cluster in patients such as cardiovascular disease, diabetes, obesity, polycystic ovary syndrome, hyperlipidemia and hypertension, as well as for preventing and treating other diseases and conditions |
| US20150335586A1 (en) | 2014-05-20 | 2015-11-26 | R.P. Scherer Technologies, Llc | Capsule dispensing container |
| US9861611B2 (en) | 2014-09-18 | 2018-01-09 | Virun, Inc. | Formulations of water-soluble derivatives of vitamin E and soft gel compositions, concentrates and powders containing same |
| WO2016044805A1 (en) | 2014-09-18 | 2016-03-24 | Virun, Inc. | Soft gel compositions and pre-gel concentrates |
| EP3053598A1 (en) | 2015-02-06 | 2016-08-10 | Faes Farma, S.A. | Calcifediol soft capsules |
| JP6019204B1 (en) * | 2015-11-30 | 2016-11-02 | 三生医薬株式会社 | Soft capsule |
| ITUB20156821A1 (en) | 2015-12-09 | 2017-06-09 | Altergon Sa | JELLY CAPSULES SPRINGS RELEASE INDEPENDENT pH |
| NL2017219B1 (en) | 2016-07-22 | 2018-01-30 | Rousselot B V | Low cross-linking gelatine |
| WO2019222100A1 (en) * | 2018-05-16 | 2019-11-21 | Zumeta Perez Javier | High concentration suspension formulation for cold and flu soft gel capsule medications |
| TW202106280A (en) * | 2019-08-08 | 2021-02-16 | 英諾美生物科技股份有限公司 | Capsule for storing lubricant |
| US11583552B2 (en) | 2021-02-17 | 2023-02-21 | Manoj Maniar | Pharmaceutical formulation of arsenic trioxide |
| EP4176724A1 (en) | 2021-11-09 | 2023-05-10 | Universität Hohenheim | Use of an oleogel as a layer or coating |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2172357A (en) * | 1938-01-29 | 1939-09-12 | Atlas Powder Co | Composition |
| GB715879A (en) * | 1952-06-23 | 1954-09-22 | Scherer Corp R P | Improvements in or relating to gelatin capsule and method of making the same |
| US2870060A (en) * | 1956-02-07 | 1959-01-20 | Mead Johnson & Co | Stable encapsulated solution of a salt of a dialkyl sulfosuccinate |
| US2870062A (en) * | 1956-04-27 | 1959-01-20 | Scherer Corp R P | Gelatin composition for capsules |
| US2889252A (en) * | 1956-05-14 | 1959-06-02 | American Cyanamid Co | Gelatin capsule containing hexylresorcinol and a lower polyalkylene glycol |
| US2847346A (en) * | 1956-11-20 | 1958-08-12 | Lloyd Brothers Inc | Laxative compositions contaqining dioctyl sodium sulfosuccinate and 1, 8-dihydroxyanthraquinone |
| DE1617629A1 (en) * | 1966-11-09 | 1971-03-25 | Merck Patent Gmbh | Process for the stabilization of bromeline in pharmaceutical preparations |
| US3520971A (en) * | 1966-12-05 | 1970-07-21 | Scherer Corp R P | Bath capsule |
| FR1599474A (en) * | 1968-12-27 | 1970-07-15 | ||
| YU36434B (en) * | 1969-05-14 | 1984-02-29 | Sanol Arznei Schwarz Gmbh | Process for obtaining gelation capsules filled with the active substance resistant to gastric juice and dissolvable in the small intestine |
| US3779942A (en) * | 1970-12-04 | 1973-12-18 | Minnesota Mining & Mfg | Capsules and process for forming capsules |
| SU432703A3 (en) * | 1971-08-24 | 1974-06-15 | Фридрих Боссерт, Вульф Фатер, Курт Бауер | |
| US4198391A (en) * | 1973-07-20 | 1980-04-15 | R. P. Scherer Ltd. | Pharmaceutical compositions |
| BE825842A (en) * | 1974-02-22 | 1975-08-21 | PHARMACEUTICAL COMPOSITIONS INCLUDING DIGOXIN | |
| US4002718A (en) * | 1974-10-16 | 1977-01-11 | Arnar-Stone Laboratories, Inc. | Gelatin-encapsulated digoxin solutions and method of preparing the same |
| US4428927A (en) * | 1981-05-11 | 1984-01-31 | R. P. Scherer Corporation | Masticatory soft elastic gelatin capsules and method for the manufacture thereof |
| US4366145A (en) * | 1981-06-24 | 1982-12-28 | Sandoz, Inc. | Soft gelatin capsule with a liquid ergot alkaloid center fill solution and method of preparation |
| CA1216793A (en) * | 1982-07-19 | 1987-01-20 | Cheng-Der Yu | Pge-type compositions encapsulated by acid isolated gelatin |
-
1983
- 1983-03-02 GB GB838305693A patent/GB8305693D0/en active Pending
-
1984
- 1984-02-27 EP EP84301238A patent/EP0121321B1/en not_active Expired - Lifetime
- 1984-02-27 DE DE8484301238T patent/DE3484779D1/en not_active Expired - Lifetime
- 1984-02-27 AT AT84301238T patent/ATE65023T1/en not_active IP Right Cessation
- 1984-02-29 JP JP59501367A patent/JPH06695B2/en not_active Expired - Lifetime
- 1984-02-29 WO PCT/US1984/000321 patent/WO1984003416A1/en unknown
- 1984-02-29 AU AU26981/84A patent/AU566832B1/en not_active Ceased
- 1984-02-29 DK DK146784A patent/DK162875C/en not_active IP Right Cessation
- 1984-03-01 CA CA000448594A patent/CA1211049A/en not_active Expired
- 1984-03-01 FI FI840832A patent/FI79244C/en not_active IP Right Cessation
- 1984-03-02 NO NO840793A patent/NO840793L/en unknown
- 1984-03-02 ES ES530270A patent/ES530270A0/en active Granted
- 1984-03-02 KR KR1019840001066A patent/KR890000117B1/en not_active IP Right Cessation
-
1986
- 1986-10-01 US US06/914,122 patent/US4780316A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| FI840832A0 (en) | 1984-03-01 |
| NO840793L (en) | 1984-09-03 |
| EP0121321B1 (en) | 1991-07-10 |
| EP0121321A2 (en) | 1984-10-10 |
| DK162875B (en) | 1991-12-23 |
| JPH06695B2 (en) | 1994-01-05 |
| FI840832A (en) | 1984-09-03 |
| FI79244B (en) | 1989-08-31 |
| DE3484779D1 (en) | 1991-08-14 |
| KR850002954A (en) | 1985-05-28 |
| DK162875C (en) | 1992-05-18 |
| FI79244C (en) | 1989-12-11 |
| EP0121321A3 (en) | 1986-01-29 |
| DK146784D0 (en) | 1984-02-29 |
| JPS60500867A (en) | 1985-06-06 |
| ES8503508A1 (en) | 1985-03-16 |
| ATE65023T1 (en) | 1991-07-15 |
| US4780316A (en) | 1988-10-25 |
| KR890000117B1 (en) | 1989-03-08 |
| AU566832B1 (en) | 1987-10-29 |
| WO1984003416A1 (en) | 1984-09-13 |
| DK146784A (en) | 1984-09-03 |
| ES530270A0 (en) | 1985-03-16 |
| GB8305693D0 (en) | 1983-04-07 |
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